Modeling the interaction of thiozonide and atphase M.tuberculosis by the method of molecular docking-Reference-Cited by-同舟云学术

Modeling the interaction of thiozonide and atphase M.tuberculosis by the method of molecular docking

Published:2021-10-26 Issue:3E Volume:17 Page:170-175
ISSN:2713-0428
Container-title:Journal Biomed
language:
Short-container-title:BIOMEDICINE

Author:

Shilov B. V.¹,Smirnov A. S.¹,Savchenko A. Yu.²

Affiliation:

1. Russian National Research Medical University named after N.I. Pirogov of the Ministry of Health Сare of Russia

2. Scientific Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia

Abstract

The mechanism of interaction of a new anti-tuberculosis drug thiosonide with a probable target of M. tuberculosis was studied. According to the data obtained, the most likely target with a thiozonide binding pocket is the subunit of bacterial ATP synthase, an enzyme that plays a key role in the processes of energy exchange in the cell, coupling the reaction of ATP synthesis/hydrolysis with transmembrane proton transfer. Original models of the three subunits of this enzyme (alpha, delta, and epsilon) were built. To simulate docking in silico, the AutoDock program version 4.2 was used, which is included in the MGL Tools version 1.5.6. It was shown that all three subunits have clusters with the minimum binding energies for the thiosinide molecule, and the epsilon subunit has two clusters with equal probabilities of being a thiosinide binding site.

Publisher

Scientific Center for Biomedical Technologies of the Federal Medical-Biological Agency

Subject

General Medicine

Reference11 articles.

1. Bocharova I.V., Burenkov M.S., Lepekha L.N., Smirnova T.G., Chernousova L.N., Demihova O.V. Doklinicheskie issledovaniya spetsificheskoy aktivnosti novogo protivotuberkuleznogo preparata tiozonid [Preclinical studies of the specific activity of the new anti-TB drug thiosonide]. Tuberkulioz i bolezni legkih [Tuberculosis and lung disease]. 2014;(6):46–50. (In Russian). DOI: 10.21292/2075-1230-2014-0-6-46-50.

2. Men’shikova L.A. Farmakokineticheskoe issledovanie original’nogo lekarstvennogo sredstva tiozonida [Pharmacokinetic study of the original drug thiozonide]: Abstract of diss. … cand. pharm. sci. Moscow, 2016. (In Russian).

3. Shadrina M.S., Rogov A.V., Bravaya K.B., Nemuhin A.V. Molekulyarnyy doking proizvodnykh guanozinnukleotidov v GTF-svyazyvayushchie belki [Molecular docking of guanosine nucleotide derivatives into GTPbinding proteins]. Vestnik Moskovskogo Universiteta. Ser. 2. Himiya [Moscow University Bulletin. Ser. 2. Chemistry]. 2005;46(6):363–369. (In Russian).

4. Diacon A.H., Pym A., Grobusch M., Patientia R., Rustomjee R., Page-Shipp L., Pistorius C., Krause R., Bogoshi M., Churchyard G., Venter A., Allen J., Palomino J.C., De Marez T., van Heeswijk R.P.G., Lounis N., Meyvisch P., Verbeeck J., Parys W., de Beule K., Andries K., Neeley D.F.M. The Diarylquinoline TMC207 for multidrug-resistant tuberculosis. N. Engl. J. Med. 2009;360(23):2397– 2405. DOI: 10.1056/NEJMoa0808427.

5. Esposito S., D’Ambrosio L., Tadolini M., Schaaf H.S., Caminero L.J., Marais B., Centis R., Dara M., Matteelli A., Blasi F., Migliori G.B. ERS/ WHO Tuberculosis Consilium assistance with extensively drug-resistant tuberculosis management in a child: Case study of compassionate delamanid use. Eur. Respiratory J. 2014;44:811–815. DOI: 10.1183/09031936.00060414.